Current Opinion in Molecular Therapeutics最新文献_第4页

OBI-1, porcine recombinant Factor VIII for the potential treatment of patients with congenital hemophilia A and alloantibodies against human Factor VIII. OBI-1，猪重组因子VIII对先天性血友病A患者的潜在治疗作用和抗人因子VIII的同种抗体。

Current Opinion in Molecular Therapeutics Pub Date : 2010-10-01

Vincenzo Toschi

{"title":"OBI-1, porcine recombinant Factor VIII for the potential treatment of patients with congenital hemophilia A and alloantibodies against human Factor VIII.","authors":"Vincenzo Toschi","doi":"","DOIUrl":"","url":null,"abstract":"Hemophilia A is caused by a deficiency in blood coagulation Factor (F)VIII. Treatment for acute bleeding in patients comprises prophylactic infusion with human plasma-derived (pd) or recombinant (r)FVIII to increase circulating FVIII levels. However, alloantibodies (inhibitor) may arise in patients, limiting the efficacy of replacement therapy, especially in patients who develop high-titer inhibitors. For these patients, FVIII-bypassing agents are proposed, but there is a rare risk of thrombotic events. Porcine pdFVIII successfully achieves hemostatic FVIII levels in patients in whom human FVIII was ineffective, but possible residual viral contamination and immunogenicity prevents routine use. OBI-1, being developed by Ipsen and Inspiration Biopharmaceuticals Inc, is a bioengineered form of porcine rFVIII that is highly purified. OBI-1 has the procoagulant and biochemical properties of porcine pdFVIII, with improvements in risk of toxicity, infection and ease of manufacture. OBI-1 demonstrated significantly less immunogenicity than pdFVIII in a murine model of hemophilia A. Moreover, in cynomolgus monkeys, OBI-1 did not generate detectable inhibitors. OBI-1 was effective in a phase II, open-label clinical trial in patients with hemophilia A and inhibitor against porcine FVIII, who were experiencing a non-life or -limb threatening bleed. OBI-1 was well tolerated, without drug-related serious adverse events and is promising for further studies.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 5","pages":"617-25"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29318248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adeno-associated virus for the treatment of muscle diseases: toward clinical trials. 腺相关病毒治疗肌肉疾病:走向临床试验

Current Opinion in Molecular Therapeutics Pub Date : 2010-10-01

Nina DiPrimio, Scott W J McPhee, R Jude Samulski

{"title":"Adeno-associated virus for the treatment of muscle diseases: toward clinical trials.","authors":"Nina DiPrimio, Scott W J McPhee, R Jude Samulski","doi":"","DOIUrl":"","url":null,"abstract":"Muscle diseases include muscular dystrophies, cardiomyopathies, neuromuscular and metabolic disorders. The loss of normal muscle structure and function is associated with significant morbidity and mortality. Patients with Duchenne muscular dystrophy usually lose ambulation in their teenage years, and frequently experience severe respiratory problems and heart failure in later stages of life. These unmet medical needs have encouraged the development of genetic strategies targeting the underlying muscle disease processes. Adeno-associated virus (AAV) vectors have been identified as promising gene delivery candidates because of their ability to transduce muscle tissue efficiently while transporting a genetic payload. There is currently significant momentum in the research of AAV-mediated delivery of muscle genes. Various AAV-based therapeutic strategies are undergoing preclinical and clinical testing, including the use of miniaturized and codon-optimized transgenes, exon skipping expression cassettes, novel tissue-specific promoters, AAV capsid mutants and chimeras, and localized intravascular administration procedures. These advancements in gene delivery have led to the generation of AAV vectors with targeted transgene expression, tissue-selective tropism and minimal off-target effects. This review describes advances in AAV gene therapy that are specific to the treatment of muscle diseases, and discusses the implications of their clinical application.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 5","pages":"553-60"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29315518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene therapy for liver cancer: clinical experience and future prospects. 肝癌基因治疗:临床经验及前景展望。

Current Opinion in Molecular Therapeutics Pub Date : 2010-10-01

Bruno Sangro, Jesus Prieto

{"title":"Gene therapy for liver cancer: clinical experience and future prospects.","authors":"Bruno Sangro, Jesus Prieto","doi":"","DOIUrl":"","url":null,"abstract":"In contrast to the large quantity of preclinical evidence for efficacy, few gene therapy agents have reached clinical development for the treatment of primary and secondary liver cancer. This review discusses the published clinical trials that have explored the feasibility, safety and efficacy of gene therapy strategies for the treatment of liver cancer. Strategies include restoration of tumor suppressor genes, genetic prodrug-activating therapy, genetic immunotherapy and oncolytic virotherapy. In these trials, transgene expression of varying degrees has been detected. Globally, gene therapy has proven to be safe, with none of the agents tested reaching the MTD. Although none of the phase II trials provided significant response rates, objective remissions have occasionally been observed and proof-of-concept for the ability of gene therapy to produce significant tumor cell killing has been determined. Insufficient delivery following intravascular administration and short-lived transgene expression are likely to be the cause of this limited antitumor efficacy. The development of new gene therapy vectors with improved characteristics will increase the probability of success of gene therapy for the treatment of liver cancer.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 5","pages":"561-9"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29315520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

tgAAG76, an adeno-associated virus delivered gene therapy for the potential treatment of vision loss caused by RPE65 gene abnormalities. tgAAG76是一种腺相关病毒提供的基因疗法，可用于治疗由RPE65基因异常引起的视力丧失。